Tunicamycin (TM), an inhibitor of dolichol-phosphate dependent protein glycosylation, has been shown to cause a photoreceptor-specific degeneration when injected intraocularly in frogs. The proposed research will examine the potential of producing a similar, specific, TM-induced degeneration in a warm-blooded mammalian duplex retina. Electron and light microscopy will be used to follow the course of the histopathology in pigmented rabbits. Parallel electrophysiological (e.g., ERG) techniques will be used to assess both rod and cone function. After establishing a dose-response curve (fixed-time procedure) for production of the degeneration, a single TM concentration (selectively toxic to photoreceptors, fixed-dose procedure) will be used to determine a time course for the degeneration. Autoradiography will be performed on eyes after intraocular injection of 3H-mannose (N-linked oligosaccharide precursor) or 3H-leucine (polypeptide precursor), to determine the effect of TM on the incorporation of these substrates into retinal cells and the retinal pigment epithelium. The presence or absence of a band of silver grains at the base of rod outer segment (ROS) and quantitation of silver grains in autoradiograms will be used to assess the effects of TM on ROS membrane assembly. These studies will provide a new mammalian animal model that may be particularly relevant to understanding the molecular events underlying certain human retinal dystrophies. Retinitis Pigmentosa, for example, has recently been linked to defects in the dolichol-phosphate dependent protein glycosylation.